Comparative Study of the Effects of Erythromycin and Roxithromycin on Action Potential Duration and Potassium Currents in Canine Purkinje Fibers and Rabbit Myocardium

Background: Erythromycin and roxithromycin are macrolide antibiotics in common clini cal use. Erythromycin occasionally produces life-threatening arrhythmias (torsades de pointes) by blocking the outward potassium current responsible for repolarization of the cardiac action potential. Methods and Results: We used standard cellular electrophysiological and whole-cell patch- clamping techniques to compare the relative efficacy of erythromycin and roxithromycin in prolonging cardiac action potential in canine Purkinje fibers and in blocking individual out ward potassium currents in isolated rabbit ventricular myocytes. We demonstrated signifi cant prolongation of action potential duration in canine Purkinje fibers by erythromycin but not roxithromycin at a concentration of 100 μM. The delayed rectifier, the outward potas sium current thought to be most sensitive to modulation by drugs, was significantly depressed by both agents at concentrations of ≥30 μM in isolated rabbit ventricular myo cytes. Both drugs had similar potencies (26% and 21 % reduction by 30 μM erythromycin and roxithromycin, respectively, and 50% and 36% reduction by 100 μM erythromycin and roxithromycin). Neither agent significantly blocked other potassium currents (including the transient outward current). Conclusions: Taking into account normally observed peak blood concentrations of these agents in clinical use and the fact that roxithromycin is not normally administered intrave nously, we conclude that the risk of proarrhythmia during normal clinical use of oral roxithromycin is extremely remote.